Treat-and-extend Using Aflibercept for Type 3 Neovascularization
试验速览
- 阶段
- 4 期
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in best-corrected visual acuity (BCVA)
研究概览
简要总结
Type 3 neovascularization is a subtype of neovascular age-related macular degeneration (AMD) that is characterized by intraretinal neovascularization. Treat-and-extend (TAE) regimen is a widely-used, effective anti-vascular endothelial growth factor treatment regimen for neovascular AMD, regardless of subtypes of AMD. The purpose of the present study is to investigate the 18-month treatment outcome of TAE in type 3 neovascularization.
详细描述
Type 3 neovascularization also called retinal angiomatous proliferation is a subtype of neovascular age-related macular degeneration (AMD) that is characterized by intraretinal neovascularization.
The incidence of type 3 neovascularization is relatively lower than other subtypes of neovascular AMD, constituting 10 to 20% of entire neovascular AMD. However, it is a very important disorder because it often leads bilateral visual deterioration. The high risk of bilateral involvement is characteristic of type 3 neovascularization. In some cases, the visual prognosis of the initially uninvolved eye with better vision, is poorer than the initially involved eye. In addition, profound visual loss may occur during the treatment course, especially in undertreated cases. Thus, preserving vision is particularly important in type 3 neovascularization, which subsequently highlights the importance of investigating more effective treatment strategies. Previous study suggested the need for proactive treatment in type 3 neovascularization to reduce the risk of abrupt visual loss.
Treat-and-extend (TAE) regimen is a widely-used, effective anti-vascular endothelial growth factor treatment regimen for neovascular age-related macular degeneration (AMD), regardless of subtypes of AMD. However, since type 3 neovascularization is at high risk of GA, there has been some debate regarding the benefit of TAE, when compared to the as-needed regimen, for treating type 3 neovascularization. Despite some controversy, reports indicated that increased injection frequency is associated with development or progression of GA. Thus, it is important to balance efficacy and efficiency when treating type 3 neovascularization.
Type 3 neovascularization is a disorder in which the treatment outcome of TAE regimen was first reported. Nevertheless, only limited evidence has been available regarding the efficacy of TAE using aflibercept in this disorder. In addition, all the previous studies were retrospective, based on relatively small study population. Moreover, results of extending the injection interval to 4 months have not yet been reported. Recently, ALTAIR study provides a scientific evidence that injection interval can be extended to 4 months when using TAE regimen. In type 3 neovascularization, extending the injection interval is not only decreases treatment burden of the patient, but also may improve long-term visual outcomes because it may decrease the injection frequency. If this regimen is found to be effective in type 3 neovascularization, it may contribute to more widespread use of TAE regimen using aflibercept for type 3 neovascularization.
In addition, there are two questions which have not been addressed in previous TAE studies for type 3 neovascularization. The first question is "Is the treatment using TAE regimen can impede the fundamental progression of the disorder?". Since visual loss in type 3 neovascularization usually develops in stage 3 disorder (eyes exhibits serous pigment epithelial detachment on OCT, it will be a very meaningful result if TAE can impede stage progression. The second question is "Is there any clues to predict the recurrence of fluid?" Since avoiding under-treatment is very important in type 3 neovascularization, it is very important to identify any factor predictive of recurrence. To address this question, it is necessary to evaluate the serial changes in vascular morphology of type 3 neovascularization lesion. Previously, however, this kind of approach cannot be performed because it requires frequent, serial indocyanine-green angiography examination. Fortunately, recent advent of OCT-angiography provides simple and safe evaluation of vascular morphology. By using OCT-angiography, any vascular morphologic changes preceding the recurrence of fluid during the TAE treatment can be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
No masking
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing, committed, and able to return for ALL clinic visits and complete all study related procedures.
- •Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) understand and willing to sign the informed consent form.
- •Signed informed consent
- •Patients aged 50 years or older
- •Patients diagnosed with treatment naïve type 3 neovascularization
- •ETDRS BCVA letter score ≥25 letters (approximately 20/320 or better) in the study eye
排除标准
- •Any prior ocular (in the study eye) or systemic treatment or surgery for neovascular AMD except dietary supplements or vitamins.
- •Prior treatment with anti-VEGF agents
- •Known serious allergy to the fluorescein sodium for injection in angiography.
- •Significant media opacities, including cataract, in the study eye that might interfere with visual acuity, assessment of safety, or fundus photography.
- •Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the patient beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety.
- •Any ocular or periocular infection within the last 2 weeks prior to Screening in either eye.
- •Any history of uveitis in either eye.
- •Presence of definite chorioretional anastomosis
- •Subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye. (If the blood is under the fovea, then the fovea must be surrounded 270 degrees by visible CNV.)
- •Scar or fibrosis, making up > 50% of total lesion in the study eye.
- •Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
- •Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.
- •History or clinical evidence of diabetic retinopathy, diabetic macular edema or any other vascular disease affecting the retina, other than AMD, in either eye.
- •Any concurrent intraocular condition in the study eye (e.g. cataract) that, in the opinion of the investigator, could require either medical or surgical intervention during the 76 week study period.
- •Prior vitrectomy in the study eye
- •Any history of macular hole of stage 2 and above in the study eye.
- •Any intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of day 1, as long as its unlikely to interfere with the injection.
- •Prior trabeculectomy or other filtration surgery in the study eye.
- •Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye.
- •Active intraocular inflammation in either eye.
- •Active ocular or periocular infection in either eye.
- •Aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye.
- •History of corneal transplant or corneal dystrophy in the study eye.
研究组 & 干预措施
Treatment arm
Patients treated with aflibercept (2.0ml/0.05cc) using treat-and-extend regimen.
Three monthly loading injections followed by proactive treatment using treat-and-extend regimen. Extension of injection interval by 2 weeks. The maximum injection interval was set as 16 weeks.
干预措施: Aflibercept Injection (Drug)
结局指标
主要结局
Change in best-corrected visual acuity (BCVA)
时间窗: From baseline to week 76
Change in early treatment of diabetic retinopathy score (ETDRS) BCVA from baseline to week 76
次要结局
- Incidence of geographic atrophy(at baseline, and at weeks 52 and 76)
- Proportion of patients who gain ≥15 ETDRS letters(from baseline to week 52 and 76)
- Proportion of patients who loss ≥15 ETDRS letters(from baseline to week 52 and 76)
- Number of injections(up to week 52 and 76)
- Proportion of patients without fluid or hemorrhage(at week 52 and 76)
- The maximum treatment interval and the maximum next planned interval(during week 52 and 76)
- Change in BCVA to wee 52 (interim analysis)(from baseline to week 52)
- Changes in size of geographic atrophy(from baseline to week 52 and 76)
- Proportion of patients showing fovea-involving geographic atrophy or fibrotic scar(at week 52 and 76)
- Change in central retinal thickness(from baseline to week 52 and 76)
- Proportion of patients showing progression of stages of type 3 neovascularization(Through study completion, 72 weeks)
- Morphologic features of type 3 lesion(Through study completion, 72 weeks)
- Proportion of patients showing tear of retinal pigment epithelium or subretinal hemorrhage(Through study completion, 72 weeks)